Obesity and disease severity magnify disturbed microbiome-immune interactions in asthma patients

David Michalovich, Noelia Rodriguez-Perez, Sylwia Smolinska, Michal Pirozynski, David Mayhew, Sorif Uddin, Stephanie Van Horn, Milena Sokolowska, Can Altunbulakli, Andrzej Eljaszewicz, Benoit Pugin, Weronika Barcik, Magdalena Kurnik-Lucka, Ken A Saunders, Karen D Simpson, Peter Schmid-Grendelmeier, Ruth Ferstl, Remo Frei, Noriane Sievi, Malcolm KohlerPawel Gajdanowicz, Katrine Bækby Graversen, Katrine Lindholm Bøgh, Marek Jutel, James R Brown, Cezmi A Akdis, Edith M Hessel, Liam O'Mahony*

*Corresponding author for this work

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Abstract

In order to improve targeted therapeutic approaches for asthma patients, insights into the molecular mechanisms that differentially contribute to disease phenotypes, such as obese asthmatics or severe asthmatics, are required. Here we report immunological and microbiome alterations in obese asthmatics (n = 50, mean age = 45), non-obese asthmatics (n = 53, mean age = 40), obese non-asthmatics (n = 51, mean age = 44) and their healthy counterparts (n = 48, mean age = 39). Obesity is associated with elevated proinflammatory signatures, which are enhanced in the presence of asthma. Similarly, obesity or asthma induced changes in the composition of the microbiota, while an additive effect is observed in obese asthma patients. Asthma disease severity is negatively correlated with fecal Akkermansia muciniphila levels. Administration of A. muciniphila to murine models significantly reduces airway hyper-reactivity and airway inflammation. Changes in immunological processes and microbiota composition are accentuated in obese asthma patients due to the additive effects of both disease states, while A. muciniphila may play a non-redundant role in patients with a severe asthma phenotype.
Original languageEnglish
Article number5711
JournalNature Communications
Volume10
Number of pages14
ISSN2041-1723
DOIs
Publication statusPublished - 2019

Cite this

Michalovich, D., Rodriguez-Perez, N., Smolinska, S., Pirozynski, M., Mayhew, D., Uddin, S., ... O'Mahony, L. (2019). Obesity and disease severity magnify disturbed microbiome-immune interactions in asthma patients. Nature Communications, 10, [5711]. https://doi.org/10.1038/s41467-019-13751-9